Human interleukin-17 (IL-17A) is a pro-inflammatory cytokine secreted by activated T-cells. IL-17A is a validated target for treatment of severe plaque psoriasis. There are six different homodimeric cytokines (IL-17A-F) and the heterodimer IL-17A/F in the IL-17 cytokine family. IL-17F is the closest homologue to IL-17A and is 50% identical in sequence. IL-17A and IL-17F are secreted both as disulfide-linked homodimers (32-38 kDa) and as the IL-17A/F covalent heterodimer (40-45 kDa). Like IL-17A, IL-17F activates immune and non-immune cells to induce pro-inflammatory mediators. These mediators can induce neutrophil recruitment at inflammatory sites, promote local tissue destruction, induce neovascularization in tumors, enhance osteoclastogenesis, and protect from pathogen infection, resulting in disease development and host protection.
IL-17A is a validated target for treatment of severe plaque psoriasis. The current approach is to block IL-17A interaction with its receptor at the cell surface by neutralizing circulating IL-17A. This is done primarily through monoclonal antibodies and fragments thereof.
IL-17 cytokine family members mediate their effects through binding to the IL-17 receptor family, of which there are five related members (IL-17RA-IL-17RE). Both IL-17A and IL-17F bind as homodimers or heterodimers to the heterodimeric receptor complex formed between IL-17RA and IL-17RC. While the activity of IL-17F appears to be related to that of IL-17A, the potency differs, consistent with differences in receptor binding affinities.
Because of their roles in immunity and immune-mediated diseases, IL-17A and IL-17F have become an area of focus in therapeutic drug development. The very low natural abundance of circulating IL-17A and IL-17A/F has been a challenge for detecting these biomarkers by traditional sandwich immunoassays. Highly sensitive detection of the circulating levels of each homodimer (IL17A, IL-17F), as well as the IL-17A/F heterodimer, would be informative for understanding the involvement of each cytokine over the course of disease and treatment.